Normal development of human skin involves proliferation and differentiation of epidermal cells. There is little evidence as to the rate of proliferation as related to gestational development or to the identification of the cells which are dividing and the cells destined to differentiate. For rodent skin and other tissues, there is evidence that only a small fraction of the proliferating cells, stem cells, have the ability to divide indefinately. These cells are responsible for providing the differentiating cells during normal turnover and growth of the epidermis and for regeneration of the tissue following damage. They may have unusual patterns of differential division. Although it is probable the stem cells exist in human fetal skin, and have important implications for fetal epidermal disease and development, they have not yet been identified. Pilot experiments have indicated that not only basal cells, but also intermediate cells proliferate during growth of fetal skin and that there is a small number of epidermal cells which have a long cell cycle and may be stem cells. The proposed research will employ techniques of lgiht and electron microscopic autoradiography, long term organ culture and cell culture to: a) determine proliferative rates of epidermal cells ar related to gestational age, b) examine organ cultures for cells with long cell cycles (LRCs), c) determine the number of LRCs as related to age of gestational development, d) investigate the clonogenic ability of LRCs in vitro and e) examine unusual patterns of proliferation of LRCs in vitro.